Acetic Acid → HCID 11715927, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-hydroxyacetophenone (1.361 g, 10 mmol) in 20 mL anhydrous pyridine was added 3,5-dimethyl-4-methoxybenzoic acid (2.162 g, 12 mmol). The mixture was cooled to 0° C. and phosphorous oxychloride (1 mL) was added. A white precipitate was formed. The reaction mixture was stirred at rt for 2 h under nitrogen atmosphere. Then the reaction mixture was poured into 100 mL cold 2N HCl and extracted with EtOAc (2×200 mL). The combined organic layers were washed with water and brine and dried over anhydrous Na2SO4. The solvent was removed under vacuum to give a colorless liquid (2.89 g, 97%), which was used in the next step without further purification. The compound (2.88 g, 9.65 mmol) was dissolved in 10 mL anhydrous pyridine. Powdered potassium hydroxide (1.62 g, 28.95 mmol) was added and the reaction mixture was stirred at rt overnight under nitrogen. Water (100 mL) was added and the mixture was neutralized to pH 7 with conc. HCl. The yellow solid was filtered off, washed with water and dried under vacuum. Yield: 1.16 g, 40%. To a suspension of the yellow solid (1.14 g, 3.83 mmol) in 8 mL glacial AcOH was added 4 drops of conc. HCl and the reaction mixture was stirred at 110° C. for 2 h. The mixture was cooled to rt and water (50 mL) was added. The solid was isolated by filtration and washed with water and dried under vacuum to give 2-(4-methoxy-3,5-dimethyl phenyl) chromen-4-one (1.05 g, 98%) as a pale green solid. 2-(4-methoxy-3,5-dimethyl phenyl) chromen-4-one was suspended in 20 mL hydroiodic acid and 8 mL glacial AcOH was added. The reaction mixture was stirred at 110° C. for 2 h. The mixture was cooled to rt. Water (100 mL) was added and the solid was isolated by filtration, washed with water and dried under vacuum. The crude compound was washed with 1:1 dichloromethane and methanol (20 mL) to give 0.763 g of 2-(4-hydroxy-3,5-dimethylphenyl)-4H-chromen-4-one (85%) as a pale yellow solid. MS (ES) m/z: 267.06 (M+1); Mp. 255-256° C.

Provenance & Evidence